5. Angiogenesis

Question 1

Recall the 3 mechanisms of vessel formation

Answer 1

1. Sprouting
2. Arteriogenesis
3. Vasculogenesis

Question 2

What is arteriogenesis?

Answer 2

Collateral growth dependent on shear stress and external factors like macrophages

Question 3

What is vasculogenesis?

Answer 3

Bone marrow progenitor cell differentiation during development

Question 4

Where does sprouting occur?

Answer 4

Small vessels

Question 5

Upon what sort of cells do pro-angiogenic stimuli act?

Answer 5

Endothelial

Question 6

Summarise the mechanism of sprouting following stimulation

Answer 6

Endothelial cells undergo conformational change - produce filopodia
Migrate towards GFs
Cells behind tip cell proliferate to push it forward
Two tip cells meet –> fusion

Question 7

How is the tip cell different from surrounding cells in sprouting?

Answer 7

Modified cytoskelton

Question 8

What is the main trigger for sprouting?

Answer 8

Hypoxia

Question 9

Describe the mechanism by which hypoxia triggers sprouting

Answer 9

Hypoxia-induced TF (HITF) is bound to a TSG called pVHL in normoxia, released in hypoxia to drive expression of VEGF gene (vasc. endothelial GF)

Question 10

Name the 5 members of the VEGF family

Answer 10

VEGF-A/B/C/D, PlGF (placental GF)

Question 11

By what is VEGF detected?

Answer 11

Tyrosine kinase receptors (VEGFR-1,2 and 3)

Question 12

What is neuropillin?

Answer 12

Co-receptor for VEGF

Question 13

Recall the 2 coreceptors for VEGF

Answer 13

Neuropillin-1 + 2

Question 14

How do tip cells stimulate the cells behind them to divide?

Answer 14

1. Tip cells express notch ligand, which binds to notch receptors on the cells behind
2. Intracellular domain of receptor cleaved = activated
3. Cleaved domain translocated to nucleus and binds to a TF called RBP-J

Question 15

What is the main driver of the cardinal notch pathway?

Answer 15

DII4

Question 16

What is the function of DII4?

Answer 16

Inhibits expression of VEGF receptor 2 in cells adjacent to tip cell, causing these cells to recognise role as dividers

Question 17

By what factor is DII4 upregulated?

Answer 17

VEGF

Question 18

What is the role of macrophages in sprout growth?

Answer 18

Stabiliser of new vessels: carve out tunnels in ECM to provide avenues for capillary infiltration

Question 19

Recall the 3 processes involved in stabilisation of new vessels

Answer 19

1. Switch off angiogenesis
2. Reform endothelium
3. Recruit neural cells